PB2279: TRIAL IN PROGRESS: ODRONEXTAMAB, A CD20×CD3 BISPECIFIC ANTIBODY, FOR THE TREATMENT OF PATIENTS WITH RELAPSED/REFRACTORY MARGINAL ZONE LYMPHOMA (MZL) – A COHORT FROM THE ELM-2 STUDY
Authors: Seok-Goo Cho, Tae Min Kim, Michał Taszner, Tsai Yun Chen, Aafia Chaudhry, Melanie Ufkin, Amulya Uppala, Ayesha Sabir, Hesham Mohamed, Srikanth Ambati, Emmanuel Bachy
Journal: HemaSphere (2023)

Topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical Background: MZL is a heterogeneous disease comprising 3 subtypes, extra-nodal MZL of mucosa-associated lymphoid tissue, nodal MZL, and splenic MZL. Treatment of R/R MZL is similar to other indolent B-cell non-Hodgkin lymphoma (B-NHL) subtypes (e.g., follicular lymphoma [FL]), comprising rituximab-based immunochemotherapy regimens that achieve an objective response rate (ORR) of approximately 45–80%. Options after progression on rituximab-based regimens include the Bruton’s tyrosine kinase inhibitor ibrutinib, which demonstrated an ORR of 46%, but a complete response (CR) rate of only 3%, in its pivotal trial in R/R MZL. Overall, limited options are available after progression on current therapies, and a need remains for more effective treatments for R/R MZL. Odronextamab is a bispecific antibody that binds CD20-expressing B-NHL cells and CD3 on T cells. In the Phase 1 ELM-1 study, odronextamab monotherapy showed antitumor activity and a manageable safety profile in a range of R/R B-NHL subtypes, including MZL (n=6; ORR 67%) (Bannerji, et al. Lancet Haematol, 2022). In the Phase 2 ELM-2 study, odronextamab elicited an ORR of 82% and CR rate of 75% in patients with heavily pretreated R/R FL (Kim, et al. ASH, 2022). Aims: Based on the positive benefit:risk profile of odronextamab in other indolent B-NHL subtypes, we aim to evaluate the efficacy and safety of this bispecific antibody in R/R MZL. Methods: ELM-2 (NCT03888105) is an open-label study of odronextamab in patients with R/R B-NHL, that comprises five disease-specific cohorts: FL, diffuse large B-cell lymphoma, mantle cell lymphoma, MZL, and other B-NHL. Each cohort will be evaluated separately, and patients will be recruited from sites across North America, Europe, and Asia-Pacific regions. The MZL cohort is planned to include 78 patients, who will receive intravenous odronextamab monotherapy until disease progression or other protocol-defined reason for treatment discontinuation. Odronextamab is administered according to a step-up regimen during the first 21-day cycle (C), consisting of 0.7 mg split over C1 Day (D) 1 (0.2 mg) and C1D2 (0.5 mg), 4 mg split over C1D8 and C1D9, and 20 mg split over C1D15 and C1D16 (0.7/4/20 regimen). The full dose of 80 mg is given QW during C2 to C4, then 160 mg Q2W from C5 onwards. If a patient achieves a CR and has a durable response for ≥9 months after the initial determination of the CR, then dosing interval will be decreased from Q2W to Q4W. Patients eligible for the MZL cohort will be ≥18 years of age; relapsed/refractory to ≥2 prior lines of systemic therapy; Eastern Cooperative Oncology Group performance status ≤1; and have adequate bone marrow function and hepatic functions. Patients with prior allogeneic stem cell transplant or CAR T treatment will be excluded. Results: Primary endpoint is ORR (Lugano classification; assessed by independent central review). Key secondary endpoints include ORR (investigator evaluation); CR rate; progression-free survival; overall survival; duration of response; safety; pharmacokinetics; and patient-reported outcomes of quality of life. As of January 2023, 19 patients with MZL had enrolled. Summary/Conclusion: The ELM-2 study will assess the activity of odronextamab monotherapy across different subtypes of R/R B-NHL, including in patients with R/R MZL who are in need of new, effective therapies. Keywords: Relapsed lymphoma, Bispecific, Non-Hodgkin’s lymphoma, Marginal zone